Lung cancer is the second (11.4%) most commonly diagnosed cancer and the first (18%) to cause cancer-related deaths worldwide. The incidence of lung cancer varies significantly among men, women, and high and low-middle-income countries. Air pollution, inhalable agents, and tobacco smoking are a few of the critical factors that determine lung cancer incidence and mortality worldwide. Reactive oxygen species are known factors of lung carcinogenesis resulting from the xenobiotics and their mechanistic paths are under critical investigation. Reactive oxygen species exhibit dual roles in cells, as a tumorigenic and anti-proliferative factor, depending on spatiotemporal context. During the precancerous state, ROS promotes cancer origination through oxidative stress and base-pair substitution mutations in pro-oncogenes and tumor suppressor genes. At later stages of tumor progression, they help the cancer cells in invasion, and metastases by activating the NF-kB and MAPK pathways. However, at advanced stages, when ROS exceeds the threshold, it promotes cell cycle arrest and induces apoptosis in cancer cells. ROS activates extrinsic apoptosis through death receptors and intrinsic apoptosis through mitochondrial pathways. Moreover, ROS upregulates the expression of beclin-1 which is a critical component to initiate autophagy, another form of programmed cell death. ROS is additionally involved in an intermediatory step in necroptosis, which catalyzes and accelerates this form of cell death. Various therapeutic interventions have been attempted to exploit this cytotoxic potential of ROS to treat different cancers. Growing body of evidence suggests that ROS is also associated with chemoresistance and cancer cell immunity. Considering the multiple roles of ROS, this review highlights the exploitation of ROS for various therapeutic interventions. However, there are still gaps in the literature on the dual roles of ROS and the involvement of ROS in cancer cell immunity and therapy resistance.
Introduction: The marine environment is a rich source of biodiversity, with several of its inhabitants producing unique and physiologically active substances. The use of marine bacterial-derived chemicals over traditional pharmaceuticals is gaining traction due to their larger variety of targets and modes of action. To circumvent the drawbacks of current therapy options, researchers have looked to marine microbes for novel and effective anti-cancer compounds. In this study, we examine one of India's least-examined coastal areas in search of novel bacterial sources of anti-cancer chemicals. Method: Soil sediments from the Indian south coast region were collected and microbes were isolated using standard methods. The microorganisms were identified using 16s rRNA sequencing, and cytotoxic extracts were further examined using GC-MS. MTT, clonogenic, and spheroid tests assessed the extract's cytotoxicity and anti-tumor efficacy. Results: Our results indicated that the bacterial isolates with potent cytotoxic activity were Bacillus drentensis and Bacillus haikouensis and had 10 and 12 potent anti-cancer and other bioactive compounds. The extracts had an IC50 of 30.08 and 109.4 µg/ml in the HCT116 cell line, respectively, and strongly inhibited colony formation. The cell cycle analysis indicated that the extract induced cell death as indicated by the subG0 peak. We also showed that these methanolic extracts induced toxicity in a 3D spheroid model indicating a strong anti-tumor activity. Furthermore, we performed molecular docking for the compounds present in the extracts to VEGFR and nucleolin and found that ergostane had favorable binding energy only to VEGFR. Conclusion: The results indicate that the ME of B. drentensis and B. haikouensis contains potent anti-cancer compounds to exhibit cytotoxic and anti-tumor activity in colorectal cancer cells.
Neurodegenerative diseases like Alzheimer’s having become a growing concern as it is difficult to cure. Tau protein is found to be playing a major role in Alzheimer’s disease and the majority of drugs that are currently on the market are not only prohibitively expensive but also come packaged with side effects that the body cannot tolerate. Repurposing existing medications is a successful and optimistic strategy that offers reduced risk and increased possibility. We aim to retrieve the existing drugs and analyze them using in-silico techniques. We have retrieved the natural products from the Selleckchem natural product library and the ability of the drug to cross Blood Brain Barrier (BBB), and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties were examined using SwissADME. The structure of Tau protein (2MZ7) was then retrieved from PDB, and molecular docking of the compounds was performed using the PyRx-Virtual Screening Tool. Initially, 92 compounds passed the ADMET screening criteria out of which the compound Ligustroflavone was found to have the most favourable binding affinity without violating Lipinski’s rule of 5 of the compounds in the library.
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